Important links between major depressive disorder/depressive symptoms and risk for cardiovascular disease (CVD) morbidity and mortality have been documented. Depression is associated with higher rates of obesity, metabolic syndrome (MetSyn) and diabetes and greater insulin resistance, indicators of metabolic dysregulation and known CVD risk factors. Depression likely contributes to CVD risk via metabolic dysregulation but precise mechanisms by which this occurs are unknown. Inflammation may play a key role. Atherogenesis, obesity, insulin resistance, diabetes, and MetSyn are known inflammatory processes, and depression has been linked with several inflammatory markers. Missing from the literature is systematic study of the association between depression and adipocytokines, secretory proteins released from adipocytes that play a critical role in the inflammatory process and are identified as highly significant in atherogenesis and metabolic dysregulation. Of specific interest in this application are adiponectin, an anti-inflammatory adipocytokine with insulin-sensitizing, anti-thrombotic and anti-atherogenic effects, and leptin, a pro-inflammatory adipocytokine intimately involved in regulation of metabolism, energy balance, and autonomic nervous system functioning. Both adiponectin and leptin are independently associated with increased risk of future cardiovascular events and increased subclinical cardiovascular disease. We will use an existing, well-characterized cohort of African-American and Caucasian women from the Study of Women's Health Across the Nation (SWAN) for our proposed research, which includes an observation cohort study (N=581) and a retrospective cohort study (N=266 without a history of CVD, diabetes or MetSyn) to examine both cross-sectional and longitudinal associations of lifetime history of depression and current depressive symptoms with adiponectin and leptin and changes in these adipocytokines over 5 years. Support is sought for assays of adiponectin and leptin from serum specimens stored in the NIA-existing SWAN Repository and for analysis and dissemination of our findings. By using an existing, well-characterized cohort with available serum specimens, we have a unique opportunity to test the novel hypotheses we are proposing in a highly cost-efficient manner. We believe this study will provide important data for future R01 efforts planned that will extend the principal investigators'research program to investigate more broadly the interrelationships of chronic stress, emotions and metabolic dysregulation. Findings have the potential to yield significant new insights regarding the impact of depression on metabolic dysregulation and cardiovascular risk in women. PUBLIC HEALTH RELEVANCE: The proposed study will examine whether depression is associated with the adipocytokines, adiponectin and leptin, bioactive molecules secreted by adipose tissue that play a critical role in atherogenesis and metabolic dysregulation, in a sample of middle-aged black and white women. Results of the study will provide significant new information on how depression affects risk for diabetes, metabolic syndrome, obesity and cardiovascular disease in women.